Pharma, Drug Discovery, Toxicology and Medicine

Rhodiola Rosea from the Selection of Traditional Applications to the

Novel Phytotherapy for the Prevention and Treatment of SeriousDiseases By Dr. Rafie Hamidpour, Dr. Soheila Hamidpour, Dr. Mohsen Hamidpour, Mrs. Mina Shahlari, Mrs. Mahnaz Sohraby, Ms. Nooshin Shahlari & Ms. Roxanna Hamidpour Shahid Beheshti University of Medical Sciences- Tehran-Iran, United StatesAbstract- Rhodiola rosea is a remarkable herbthat has been a part of traditional medicine systems in orderto stimulatethe nervous system, toprotect thebody against oxidative stress, free radical damage,inflammation, and virus infection. Rhodiola rosea is included among a class ofplant derivatives calledadaptogen,an agent thathelps the body adapt to various stressors. Adaptogens have been claimed totreata wide variety of medical conditions, fromfatigue to cancer. The studies on Rhodiola rosea have shown that the planthas anti-stress, anti-anxiety, anti-fatigue,andanti- depressant properties with no significant side effects. Rhodiola rosea has beenconsideredin drug development because of its pharmacological activities throughout the world, especiallyin parts of Europe, Asia, and Russia. Rhodiola Rosea has shown more efficiency and safety thanpharmaceutical drugs for anxiety and depression, which typically can have side effects, such as digestiveupset, mood and sleep disorders.Keywords: antifatigue, antidepressant, alzheimer’s disease, cancer and memory enhancement.GJMR-B Classification : NLMC Code: WB 925

RhodiolaRoseafromtheSelectionofTraditionalApplicationstotheNovelPhytotherapyforthePreventionandTreatmentofSeriousDiseases Strictly as per the compliance and regulations of:

2 015 YearAbstract- Rhodiola rosea is a remarkable herb that has been a pharmaceutical drugs for anxiety and depression, whichpart of traditional medicine systems in order to stimulate the typically can have side effects, such as digestive upset,nervous system, to protect the body against oxidative mood and sleep disorders. 1stress, free radical damage, inflammation, and virus infection. This research paper, suggests that Rhodiola rosea,

Rhodiola rosea is included among a class of plant derivatives in addition to cure common disorders such as depression,called adaptogen, an agent that helps the body adapt to binge eating, anorexia, generalized anxiety disorders, andvarious stressors. Adaptogens have been claimed to treat a physical and mental fatigue, might contribute to prevent,wide variety of medical conditions, from fatigue to cancer. reduce and treat serious diseases such as Alzheimer’s The studies on Rhodiola rosea have shown that the disease, Parkinson’s disease, cardiovascular disease,plant has anti-stress, anti-anxiety, anti-fatigue, and anti- diabetes, and cancer. The aim of our future research is todepressant properties with no significant side effects. extract Rhodiola rosea into the filtration equipment and then,Rhodiola rosea has been considered in drug development with purification and extended quality control, produce tabletsbecause of its pharmacological activities throughout the for the animal trails.world, especially in parts of Europe, Asia, and Russia. Keywords: antifatigue, antidepressant, alzheimer’sRhodiola Rosea has shown more efficiency and safety than disease, cancer and memory enhancement.

Golden root, King’s crown, Lignum rhodium, Orpin rose,

R hodiola rosea, also known as golden root or “arctic root” is used as a general name, however; arctic Lignum rhodium, is a perennial herbaceous plant root is actually a trademark name for the specific in the Crassulaceae family which has been used commercial extract. as a natural medicine from ancient times. This III. Chemical Composition perennial plant reaches a height of 30-70 cm with a thick rhizome and yellow, fragrant flowers. It is a The phytochemical analysis of the Rhodiola remarkable herb that is valued in traditional medicine species has shown that the major beneficial in Eastern and Northern Europe, Asia, China, and components include salidroside and tyrosol, which are Russia for its unique pharmacological activity.[1] The rich in the rhizomes.[7] The dried rhizomes contained plant has been categorized as an “adaptogen“ by 0.05% essential oil. Terpenes and volatile compounds 2 015

Russian researchers due to its ability to elevate body have been isolated from Rhodiola rosea. As shown in resistance to physical, chemical or biological stressors, Table 1, Myrtenol (36.9%), trans-pinocarveol (16.1%), Year

treat fatigue, promote longevity, and support cognition geraniol (12.7%), Cumin alcohol (12.1%), Linalool and mood wellbeing.[2] Rhodiola rosea (SHR-5 extract) (2.7%), Perilla alcohol (1.7%) and dihydrocumin 2 has been indicated as an adaptogen in the situation of alcohols (12.1%) are the most abundant volatiles fatigue, poor mental performance and depression.[3] detected in the oil.[8] Geraniol and Myrtenol areGlobal Journal of Medical Research ( BD ) Volume XV Issue III Version I

Rhodiola rosea phytochemical extracts, are the source responsible for the rose like odor of the plant. A total of important biological activities which is used widely number of 86 chemical compounds were identified in the treatment of a wide range of diseases like in R. rosea roots. The principal components are those of the nervous and cardiovascular systems, phenylpropanoids (rosavin, rosin, and rosarin), Alzheimer’s and Parkinson’s disease, cancer, Phenylethanoids (salidroside, ρ-tyrosol) and a and inflammatory diseases.[4] The studies of monoterpene (rosiridin) which are responsible for the pharmacological activities of R. rosea have revealed pharmacological effects of R. rosea.[8,3] Rosiridin has its hepato-protective and Monoamine oxidase A (MAO- attracted particular interest because of its effect in A) inhibitory effects, in addition to the antiviral and depression and senile dementia. Rhodioloside and antibacterial activities of this plant.[5] salidroside active principles of the SHR-5 extract were Phenylethanoid (salidroside, ρ-tyrosol), found to have neuro-, cardio- and hepato- protective phenylpropanoid glycoside (rosarin, rosavin, rosin) and activities and can be effective in the prevention of a monoterpene (rosiridin) are responsible for the number of disorders related to neuro-endocrine and bioactivity of R. rosea. Salidroside, rosarin, rosavin, immune system. Three rosavin compounds (rosavin, rosin, and ρ-tyrosol are the most critical plant rosin, and rosarin) which are unique to R. rosea (the constituents used for therapeutic activities. Salidroside most used species of Rhodiola genus) might be and ρ-tyrosol have been found in all Rhodiola species responsible for antidepressant, anticancer, but the other active glycosides: rosavin, rosin, and neurotropic, and hepato- protective effects of this rosarin have not been detected in other genus of herb.[3] Rhodiola species. The compound rosavins (rosavin, rosin, and rosarin) are the compounds that contain the highest percent of R. rosea, which was not identified in other species. The compound salidroside is the most biologically active compound which shares many of its effects with rosavin.[5,6] The absence of adverse drug interactions and side effects associated with R. rosea in the clinical trials make it possible to be used as a safe medication. Rhodiola rosea also can be applied as an adjuvant to enhance therapeutic effects of Ref: [8] J Essen Oil Res 2005; 17(6):628-9. other medicines in a number of disorders such as a) Antioxidative effect chronic pneumonia, chronic tuberculosis, vascular The imbalance between reactive oxygen dystonia, cancer (reduction of metastasis), and in species (ROS) generation and antioxidant defense reducing the debilitating effects of radiotherapy and mechanism causes oxidative damage to the chemotherapy.[3,5] proteins, membrane lipids and nucleic acids in the II. Common Names cells. The increased generation of ROS damages the mitochondria, the power house of the body, which Rhodiola rosea has numerous common names. account for reducing the ability of maintaining energy Some of the best known names include Arctic root, at the cellular level and results in muscular atrophy and

Rhodiola Rosea from the Selection of Traditional Applications to the Novel Phytotherapy for the Prevention and Treatment of Serious Diseases

muscle fatigue, leading to the decreased performance cytotoxicity effect of polyphenols on tumor cells areof an individual.[9] induced by reaction oxygen species (ROS) mediated Antioxidants are natural substances that mechanisms. Polyphenols including tannins and gallicprevent or delay some type of cell damages and acids, induce apoptosis in tumor cells by increasingprotect the body against the oxidative stress and free intracellular peroxides. [15,16] The results show thatradicals. Various Rhodiola species have shown salidroside, a component isolated from plants thatsignificant antioxidant activities. Among the 28 different belong to the Rhodiola genus, causes growthcompounds identified in R. rosea, P-tyrosol, inhibition in several human cancer cell line insalidroside, and five salidroside-like glycoside concentration between 1µg/ml and 32µg/ml dose(Rhodiolin, rosiridin, rosarin, rosavin, and rosin), dependently by induction of G1-phase and/or G2-possess strong antioxidant activities.[10] phase arrest. A number of studies have investigated Polyphenols in R. rosea neutralize oxidative the inhibitory effect of salidroside on the growth ofreactions, which are induced by free radicals since stomach adenocarcinoma cells, leukemia cells, and

2 015they are excellent donors of protons and electrons. parotid carcinoma cells in vitro. In a few studies

YearIn addition, polyphenols, due to thier metal chelating performed in China, was found that Salidrosideproperties, are able to decrease oxidative stresses, could inhibit tumor-induced angiogenesis in mice.[17]induced by transition metals.[12] Breast cancer is the most common cancer 3 Salidroside (SDS), a major component diagnosed in women in the United States. It develops by

extracted from Rhodiola rosea, is a glucoside of tyrosol the mammary cell proliferation induced by estrogen.which possess a broad spectrum of pharmacological Resistance of estrogen receptor negative (ER-) tumorsproperties including strong antioxidant activity. to anti-hormone therapy is the main concern in breastSalidroside induces its antioxidant effects to the cells cancer treatment. Investigations of the effects ofby preventing collection of intracellular ROS, restoring salidroside on the breast cancer showed its inhibitorythe impaired mitochondria function and mitigating properties on human breast cancer MDA-MB-231 cells.oxidative-stress-induced apoptosis.[11] The result indicated that salidroside in concentration Production and detoxification of Reactive between 5µm and 80µm dose dependently induced cell-Oxygen Species (ROS) are of major importance in cycle arrest and apoptosis cell death in ER-negative andregulation of erythropoiesis (formation of red blood ER-positive tumors in human breast cancer.[18]cells). Salidroside plays an essential role in maintaining Thyroid cancer is the most frequent endocrinenormal erythropoiesis through the up-regulation of neoplasia and accounts for about 2% of cancer-relatedantioxidant defense mechanism. Salidroside could deaths. Management options for thyroid cancer includemediate its effect as blood tonic supplement and total or near total thyroidectomy, radioiodine therapyadaptogen. Patients with anemia and malhypoxia can and pharmacotherapy. These patients may havetake advantage of SDS as an adjuvant for neuropsychological concerns such as depressiveerythropoietin (EPO) or other erythropoiesis-stimulating moods or developed cardiovascular problems such asagents. This compound also defends erythroblasts hypertension, electrocardiogram abnormalities, andagainst oxidative stress through up-regulating the diastolic dysfunction. In numerous studies, R. rosea hasexpression of antioxidant molecules, glutathione demonstrated CNS stimulating, neuro-, cardio-peroxidase, and thioredoxin, and it also nullifies protective and antidepressant effects. Since most ofischemia-induced cardiomyocyte death through these symptoms are in fact the clinical aspect ofsuppressing ROS overgeneration. [11,13] hypothyroidism, Rhodiola rosea is recognized to aid in patient preparation during the hormone withdrawalb) Effect on cancer cells period. Oxidative stress increases when thyroid Cancer is a class of diseases characterized hormones are missing during hypothyroidism. Studiesby out-of-control cell growth. Complete eradication of in rats reveal that supplementation with R. roseacancer without damage to the rest of the body is the extract can protect cells from oxidative injuries in dose-goal of the treatment. Some plant extracts that indicate dependent manner. This finding has also beenpotential as an anticancer agent have shown to be replicated in human. Rhodiola rosea have potentiallyuseful for the treatment or prevention of the cancer additional benefits as an adaptogen that tends to be awith minimal toxicity, and they act synergistically with regulator, having normalizing effects on the organism.cytostatic to reduce their toxicity. The study showed Hypothyroidism can be considered as a stressor andthat the use of R. rosea extract in combination with the then R. rosea as an adaptogen that could help theantitumor agent cyclophosphamide increased the anti- organism’s responding.[19]tumor and antimetastatic efficacy of the drug.[14] The results of investigation in vivo show that c) Alzheimer’s DiseaseR. rosea extract has cytotoxic effect on tumor cell line Alzheimer’s disease (AD) is a progressivethrough its major component, polyphenols. The brain disorder characterized by the memory and

Rhodiola Rosea from the Selection of Traditional Applications to the Novel Phytotherapy for the Prevention and Treatment of Serious Diseases

cognitive impairments. Neuropathologically, AD is capacity required in fight to fight situation to help the defined by the accumulation of amyloid plaques and body to adapt and resist physical, chemical, and neurofibrillary tangles in certain region of the brain environmental stresses.[22,23] which are important in memory and can cause the loss Clinical efficacy of adaptogens in behavioral of synaptic connection between cells. One of the most and mental disorder has been reviewed. It is now important parts of unraveling the AD mystery is accepted that adaptogens have shown anti-fatigue, discovering what causes the disease. It has been anti-depressant, anxiolytic, nootropic, and CNS suggested that oxidative stress and dysfunction of stimulating effects. Adaptogens do not possess any neurogenesis play important roles in pathogenesis of side effects of conventional drugs such as addiction, AD.[20] Beta-amyloid (Aβ) peptide, the hallmark of tolerance and abuse potentials, or impair mental Alzheimer disease induces an oxidative damage to function, neither do they cause psychotic symptoms with neurons and finally causes neurons death. Reduced long term use.[24] levels of anti-oxidative activity have been observed 2 015

Neuro-degenerative disorders characterized by

in the specific regions of the central nervous system of the progressive loss of structure or function of neurons Year

AD patients. in the brain region involved in learning and memory.

Now researchers are paying great efforts to Rhodiola rosea as an adaptogen could induce a 4 find potent natural antioxidant with neuroprotective positive effect in neuro-degenerative disorders due to potentials. Salidroside, an active compound occurring their inhibitory effects on the formation of p-SAPKGlobal Journal of Medical Research ( BD ) Volume XV Issue III Version I

naturally in Rhodiola rosea L. is protective against (Aβ)- (phosphorylated stress-activated protein kinase). induced oxidative stress by the induction of antioxidant Related data may be considered to add further enzymes, thioredoxin (Trx), heme oxygenase-1 (HO-1), support to the hypothesis that adaptogens have and peroxiredoxin- 1(Prxl); the down regulation of pro- beneficial effect on mental performance and cognitive apoptotic protein Bax and the up regulation of anti- function.[22] The key point of action of adaptogens on apoptotic BcL-X1. Pathophysiology of neurodegerative stress appears to be related to the regulation of diseases such as AD has shown that Aβ is associated homeostasis via hypothalamic-pituitary-adrenal axis and with ROS generation which leads to mitochondrial regulation of molecular chaperones, stress-activated c- dysfunction, lipid peroxidation and apoptosis. Exposure Jun, N-terminal protein kinase, forkhead box O to ROS also inhibits neurogenesis, which is the onset transcription factor DAF-16, cortisol, nitric oxide (NO) of cognitive impairments and memory deficits. and beta-endorphin.[24] The optimal corticosteroid level Salidroside could decrease the intracellular ROS level is required for efficient cognitive function. Significant and restore the abnormal mitochondrial membrane changes (up or down) in circulating levels of potential (MMP). The neuroprotective effect of corticosteroids have been accepted as the reason for Salidroside may offer long-term protection in the cognitive impairment. Regulatory effects of R. rosea pathogenesis of AD.[20,21] on the basal level of salivary cortisol results in an d) Adaptogenic and antifatigue effects improvement in cognitive function.[3] Adaptogens are unique group of herbal Rhodiola rosea combines well with other ingredients which help strengthen the body’s adaptogens and tonics in appropriate dosages. The response to stress, enhance its ability to cope with herbal drug ADAPT-232 is based on the synergistic anxiety, and fight fatigue. They have the unique ability effect of the three most efficient adaptogen plants, to adapt their function according to the body’s specific Rhodiola rosea, Schisandra Chinensis and needs and do not disturb bodily functions at normal Eleutherococcus senticosus in a fix combination. levels. Rhodiola rosea is known as a plant’s Administration of single and repeated doses of ADAPT- adaptogens because it possesses anti-fatigue and 232 has been shown to increase physical energy as anti-stress activities that can increase mental and well as mental performance and cognitive function.[25] physical working performance against a background ADAPT-232 significantly increases secretion and of fatigue or stress.[22] The phenylpropanoid glycoside release of stress hormones, neuropeptide Y (NPY) and called salidroside, flavonoids, Phenolic, Heat Shock Protein 72 (Hsp 72) which increase polyphenolic, and flavolignas are thought to be the tolerance and adaptation to stress. These pathways main components of stress- protective and adaptogens contribute to the anti fatigue effect of ADPAT, increase of Rhodiola rosea. Other constituents isolated from R. the attention and improve the cognitive function.[24] rosea, including rhodioniside, rhodioloside A-E, Furthermore, a number of studies have rhodiolin, rosin, rosavin, rosarin, rosiridin, rosiridol, investigated the effects of ADAP-232 on pneumonia rhodalgin, acetylrhodalgin, and lotaustralin, might also patients. Clearly, adjuvant therapy on pneumonia be responsible for R. rosea’s stimulant or adaptogenic patients with ADAPT-232 has a positive effect on the effects. Such compounds can play an active role in recovery of the patients, by decreasing the duration of increasing energy, stamina, strength and mental the acute phase of the illness, increasing mental

Rhodiola Rosea from the Selection of Traditional Applications to the Novel Phytotherapy for the Prevention and Treatment of Serious Diseases

performance of the patients during the rehabilitation transferase).[4,3] General anxiety disorder (GAD) is aperiod and by improving their quality of life.[25] common disorder that involves chronic worrying, nervousness and tension. There are different types ofe) Anti-depressant and general anxiety medication for GAD, including antidepressants, Depression is a severe despondency and Benzodiazepines, and serotonin reuptake inhibitors.sadness accompanied by a feeling of desperation and Patients who do respond to conventional treatmentinadequacy. The mechanism of depression is complex. often experience adverse side effects that mayThe therapeutic effects of anti-depressants such as interfere with their consistency. Rhodiola rosea is safeTricyclic antidepressants (TCAs), Monoamine oxidase and tolerable alternative medicine. Administration of R.inhibitors (MAOLs) and Selective serotonin reuptake rosea in dosages of 2-3 capsules each containing 100-inhibitors (SSRIs) come with a number of side 170 milligrams daily approximates to the perfect dose toeffects like psychomotor impairment and gain beneficial effects.[29]dependence liability.[26]The use of Alternative Medicine

2 015especially natural products for the treatment of mental f) Anti-inflammatory and neuroprotective effectdisorders have been increased in the U.S and In general, inflammation is a localized reaction

Yearworldwide. The most common reason for people to of the body tissues to infections, irritation, injuries, oruse complementary therapies is that they want to disorders of the immune system which produce 5avoid the common side-effects of prescription anti- redness, warmth, swelling, and pain. As we age, thedepressant drugs. A few natural psychotropics have level of inflammatory immune cytokines increases and

been more extensively examined in well-designed, we get vulnerable to a number of inflammation-linkedplacebo-controlled, double-blind studies. Rhodiola diseases, such as cancer, arthritis, muscle weakness,rosea is one of these second-tier natural products fatigue, sleep disorder, Alzheimer’s and Parkinson’sfor mood disorders.[27] The standardized extract SHR-5 disease. An enormous amount of research has(3%rosavin and 0.8% salidroside) from R. rosea have a demonstrated the link between chronic low-level brainsignificant antidepressant activity in mild to moderate inflammation and elevated brain glutamate levels,depression. The symptoms evaluated were emotional which are a neurotransmitter normally involved ininstability, decreased motivation, cognitive complains learning and memory. In some cases, glutamate canand susceptibility to stress.[28] Significant improvement be an excitotoxin that is involved in nerve-cell deathin the overall symptom of depression and mood in various neurodegenerative disorders includingdeficiencies was observed in a 6-week monitoring Alzheimer’s and Lou Gehrig’s disease. Glutamate notstudy in Sweden, which R. rosea was given daily only influence amyloid β production (the cause ofwith a dosage of two tablets a day, each containing Alzheimer’s disease), but also amyloid β can change the170mg of the extract.[28] The role of serotonin, a levels of glutamate in the brain which increase themonoamine neurotransmitter, is usually known and vulnerability of cortical neurons to glutamate cytotoxicity.associated with depression, however, serotonin also It has been shown in several studies that R. rosea couldhas some cognitive functions, including the improve inflammation and neurotoxicity in corticalenhancement of memory and learning. Regulation of neuronal cells. Rhodiola rosea modulates the neuronalserotonin at synapses is a major mechanism of action over action and endogenous anti-inflammatory.[30]possibly contributing to pharmacological Microglia, a type of glial cell, acts as the first andantidepressants. Central and peripheral serotonin levels main form of active immune defense in the centraldecreases in patients with depression. Monoamine nervous system (CNS), and thus plays a key role in theoxidase type A has an important role in degradation of inflammatory reaction. Inflammatory process, in thebiogenic amines such as epinephrine, norepinephrine, central nervous system leads to neuronal cell death,and serotonin. Monoamine oxidase inhibitors (MAOls) and inflammatory response is mediated by the activatedprevent the breakdown of monoamine microglia, which remove the damaged cell byneurotransmitters including serotonin and therefore phagocytosis. The chronic activation of microglia may inincreases the concentrations of neurotransmitter in turn cause neuronal damage through the secretion ofthe brain. MAOls therapy with synthetics drugs are cytotoxic molecules such as proinflammatory cytokinesknown to interact negatively with other medications and (interleukin-1ß (IL-1), IL-6 and TNF-a), proteases, andeven with food. MAOls can cause death if they are reactive oxygen species (ROS), and nitric oxidetaken in overdose extent. There is evidence that R. (NO). Therefore, suppression of microglia-mediatedrosea acts as monoamine oxidase inhibitors and inflammation can appear to be the most promisinginfluences the level and activity of biogenic option in neurodegenerative disease therapy. Sincemonoamines such as serotonin, norepinephrine, and overproduction of NO plays an important role indopamine in the nerve terminal. Rhodiola rosea inhibits neuroinflammatory disease, the effect of the R. rosea onthe activity of the enzymes responsible for monoamine nitric oxide production was investigated indegradation (monoamine oxidase and catechol-0 methyl lipopolysaccharide (LPS)-induced microglia cells.

Rhodiola Rosea from the Selection of Traditional Applications to the Novel Phytotherapy for the Prevention and Treatment of Serious Diseases

Rhodiola rosea has shown to strongly inhibit NO from hypoxemia. Since salidroside also has shown production and the expression of Inducible nitric oxide antiviral activities against CVB3 in vitro, the findings synthase (iNOS), the key enzyme for NO in LPS- have significant implications for a potential therapeutic stimulated microglia cells.[30] agent for treatment of viral myocarditis and influenza virus infections which is worthy of further future g) Antiviral activity researches.[32] The influenza is an acute infectious disease caused by an RNA virus of the family h) Antidiabetic orthomyxovirus. Influenza virus infects the epithelial cells The anti-diabetic effects of dietary of respiratory tract that causes acute pulmonary administration of Rhodiola-water extract on diseases. Influenza outbreak usually occurs in winter, streptozotocin (STZ)-induce diabetes rat model were killing numerous people in pandemic years. The investigated. STZ is a toxin with the ability to damage epidemic outbreaks of influenza are associated with pancreatic beta cells, resulting in hypoinsulinemia and 2 015

influenza virus type A and B. Type C virus is hyperglycemia. The study used STZ mice as a associated with minor symptoms. Two neuraminidase model because it is considered an appropriate Year

inhibitors have been approved by FDA (zanamivir and model to assess mechanisms of diabetes and evaluate oseltamivir) to treat influenza virus infection. Both of potential therapies. Three days administration of 6 these inhibitors are active against influenza virus A and Rhodiola-water extract in STZ-diabetic rats resulted in B, however, they have several toxic effects in the an increase of glucose transporter subtype 4(GLUT 4) inGlobal Journal of Medical Research ( BD ) Volume XV Issue III Version I

critical for diverse biological processes specifically k) Effect on Binge eating and Anorexialongevity and stress resistance. Rhodiola rosea induce Binge eating (BE) and Anorexia Nervosa aretranslocation of the DNF-16 transcription factor from official eating disorders. Binge eating appears to bethe cytoplasm into the nucleus. DAF-16 in the characterized by extreme overeating withoutnucleus reprograms the transcriptional activities subsequent purging episodes, usually secretive, andfavoring the transcription of a large number of genes filled with shame.[37] Topiramate or sibutramine areinvolved in stress resistance and longevity. [35] medications that have been suggested to reduce BE. Moreover dietary conditions are another However, their uses are associated with a variety ofhypothesis for anti aging effect of Rhodiola rosea. adverse side effects which causes serious problems,The effect of R. rosea supplement on the lifespan of such as cardiovascular disorder and stroke. As afruit fly depends on diet composition particularly on the result they have been withdrawn from the market inprotein-to-carbonate ratio. Dietary compositions with many European countries. Since stress is a key factorthe protein-to-carbohydrate ratio less than 1 extends in BE, a reduction of stress response might show an

2 015the lifespan by 15% to 21%, but diets with high effective mechanism for the treatment of BE. Therefore,

Yearprotein-to-carbohydrate ratio or high caloricity do not due to its anti-stress properties, the effect ofsupport the beneficial action of R. rosea on longevity.[36] Slidroside, an active principle of the dry extract of R.Hormesis is favorable biological responses to a low rosea, was evaluated for treatment of BE. Studies have 7dose stress-induced stimulation resulting in shown that Salidroside abolishes BE by suppressing

biologically beneficial effects on growth, reproduction the activation of hypothalamic-pituitary- adrenal (HPA)and longevity. Hormesis activates defense systems of axis, leading to a reduction of serum corticosteronethe body and the defense process repair the damage flowing chronic treatment.[1]caused by the toxin and also protect body against any Furthermore, new evidence shows that R.additional stress. It can be hypothesized that the plants rosea may cancel out the anorexia (out of controladaptogen like R. rosea act as a mild stressor leading dieting), another troubling manifestation of stress.to activate an adaptive response which protects the Eating disorders are associated with stresscells from stressful environments and increase the life responses depending on the intensity of stress itself;span. In this way, it can be mentioned that moderate stressors stimulate eating while acuteadaptogen acts as hormetic agents. The findings of a stressors, which cause high levels of CRFstudy support the view that low doses of R. rosea (corticotrophin-releasing factors), induce anorexia. Inextract (10-25µg/ml) works in a deliberate and particular, considerable evidence suggests a role forsystematic way in order to increase the stress endogenous brain CRF system in appetite regulationresistance and lifespan of C. elegans between 10 and and the cause of eating disorder. At doses of 1520%, whereas the higher doses tested (250µg/ml) of and 20mg/kg, Rhodiola extract significantly inhibits theRhodiola showed a life span shortening of 15 to 25 anorexia effects of stress within 60 minutes after apercent. [35] single oral administration of R. rosea extract.[38]j) Cardioprotective effects Therefore, the different effects evoked by R. rosea on Hyperhomocysteinemia (high homocysteine eating behavior could be attributed to its ability tolevel in the blood) is a major risk factor of cardiovascular modulate the activation of several components ofdisease. An abnormal accumulation of homocysteine, stress-response system rather than a direct effect onan amino acid that is produced by human body due to orexigenic or anorexigenic mechanisms.[1]consuming meat, is related to various cardiovascular l) Effect on Parkinson’s Diseasediseases such as coronary heart disease, stroke and Parkinson’s disease (PD) is a chronic andperipheral vascular disease (fatty deposits in peripheral progressive disorder of the nervous system that affectsarteries). Homocysteine exert its adverse effect on movements of the body and the symptoms continueendothelial function by increasing superoxide and worsen over the time. Parkinson’s primarilyproduction and decreasing the activity of nitric oxide affects neurons in the area of the brain calledsynthase. Homocysteine could be a starting point for the substantia nigra. Cells within the substantia producedevelopment of atherosclerosis by disturbing vascular and release dopamine, a neurotransmitter thatpermeability, damaging the inner lining of the arteries controls the movement and balance. In patientsand promoting blood clots. Slidroside extracted from suffering from Parkinson’s, the amount of dopamineRhodiola protect rats aortas against homocysteine- produced in the brain decreases. The shaking or tremorinduce impairment of endothelium by inhibiting NOX2-dependent ROS overproduction. These results suggest may begin to interfere with the daily activities of the PDthat salidroside significantly inhibit ROS overproduction patients. As these symptoms become moreassociated with vascular dysfunction, a common pronounced, patients may have difficulty walking,pathological process in hypertension and diabetes.[11] talking or performing other simple tasks. Although

Rhodiola Rosea from the Selection of Traditional Applications to the Novel Phytotherapy for the Prevention and Treatment of Serious Diseases

there is no cure, there are treatment options such as nervous system and decreasing mental and physical medication and surgery to control the symptoms.[39] fatigue. It has been shown in pharmacological The new plant preparation Phytomix-40(PM-40) investigations that, R. rosea possess antioxidant, is developed for the treatment of Parkinson’s disease. antiaging, anti-cancer and anti-cardiovascular disease Phytomix (PM-40) is a mixture of natural extracts of properties. As a dietary supplement, numerous 40 medical plants, including extracts of R. rosea, preparations of extracts are used worldwide including Eleutherococcus, ginseng, and other adaptogens with teas, homeopathic preparations and tinctures as well as neuroprotective properties. Animal experiments standardized extract. Rhodiola rosea has enormous demonstrated that PM-40 had a low toxicity. The traditional and pharmacological use in supporting mood neuroprotective plant adaptogen can be used in and cognitive function. complex therapy for the Parkinson’s disease for Rhodiola rosea is a versatile, safe and easily improving its efficacy. Oral administration of 10% accessible plant which offers resistance to the physical, solution of Phytomix-40 to mice with MPTP-induced chemical and biological stressors without interacting 2 015

Parkinson’s syndrome reduces the severity of rigidity with other food or drugs. The remarkable therapeutic Year

and increase motor activity. The preparation effects of this plant in prevention and treatment of normalized immunobiological parameters in PD patients variety of human diseases, makes this plant very 8 and relieved the clinical symptom of the disease. The valuable for further investigation in the area of mechanism of action of PM-40 contributes to the pharmaceutical industries.Global Journal of Medical Research ( BD ) Volume XV Issue III Version I